We use laser capture microdissection to isolate ultra pure populations of primary tissue for subsequent analysis. These biopsies are acquired under mpMRI-ultrasound fusion guidance. For patients enrolled in active surveillance studies, we are using exome sequencing, transcriptome sequencing, and ATAC-seq to identify differences between patients whose cancer progresses over time versus those that remain stable on imaging (and by PSA measurements). For patients enrolled in neoadjuvant intense androgen deprivation therapy clinical trials, we are using whole exome and whole transcriptome sequencing to identify the baseline characteristics that distinguish patients whose tumors respond to therapy from those who do not. Finally, in patients receiving first-line radiation therapy (with or without hormones) we are using whole exome sequencing and Affymetrix microarray analysis to correlate with radiation response on imaging and biochemical-recurrence free survival rates.